Is there any evidence that human bodies have systemic self-destruction built into their developmental program? I'm not talking about the cell death response, which I know is an important part of growth, development and cancer prevention.

I've read some things about telomere-shortening but don't know if this is a cause or an effect.

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From a certain point of view you could argue that our bodies have an inherently limited lifespan;

Telomeres are extensions to the end of chromosomes that prevent damage or loss of genetic information during cell division. Telomeres are not replaced (in normal cells), which gives rise to a replicative lifespan; the number of times a cell can divide before permenantly leaving the cell cycle (senescence).

This is generally viewed as an anti-cancer mechanism to protect against errors creeping in to the genome through many cell divisions. In order to become cancerous, a cell must first overcome its replicative lifespan [ref.]. This is achieved by activating the (normally inactive) telomerase enzyme that extends the telomeres - embryonic stem cells are one of the few cell types that normally express this enzyme.

There are other ways in which you could argue that our lifespans are fundamentally limited, but it is important to note that the objective is not 'to die', but to increase fitness (in a Darwinian sense) earlier in life. This is known as antagonistic pleiotropy; when an advantageous trait early in life is disadvantageous later in life.

Telomere shortening is just one example of antagonistic pleiotropy (protects against cancer when younger, but limits the number of times your cells can divide).

Other traits that inherently limit lifespan include;

Neurons (as a rule) do not replicate, and last for your whole life time. This certainly excludes them from replicate senescence, however it means they are highly susceptible to 'wear and tear'; oxidative stress is a natural by-product of respiration, and the vast majority of damage done by these species (e.g. reactive oxygen species) is repaired by the cell, however some will always remain unchecked, and eventually this leads to neurological dysfunction and cognitive decline. Without intervention this is inevitable in each individual (the rate of aging differs between people, but aging and age-dependent diseases are disorders are a natural part of living).

The same is true for cardiac and smooth muscle - whilst much repair can be carried out, it is inevitable that damage will creep in over a life time, and thus the vast majority of human age-related deaths are due to cardiac problems in one way or another.

So there is no 'programmed' limit to life span, in that we have not evolved to die, but our bodies are inherently limited by the systems that have evolved. Life expectancy a few thousand years ago was ~20 years (if you lived beyond infancy!), whereas now in the developed world this is ~80 years, so our bodies can already survive way beyond our 'natural' life span, and thus we now succumb to age-related disease. Evolution has spent millions of years giving us every possible advantage that leads to reproductive success. Natural selection of traits beyond reproduction are secondary to those beforehand, and thus we have fundamentally limited life spans.

There is an argument for an evolutionary advantage of limited lifespan. This seems at first counter-intuitive, until you consider that natural selection does not act on individuals, but genes. It is proposed to be advantageous (in some circumstances) for an organism to have a shorter life span, as this increases the turn-over of individuals in that population. This in turn increases their evolvability - clearly advantageous for the gene(s) influencing this trait if it increases the likelihood of successful reproduction and thus passing on that gene/allele/trait...

I like this hypothesis, and can see that natural selection may favour it. I think mice are great examples here; they have much shorter lifespans than us, yet they 'age' (biologically) the same (cardiac problems, diabetes, cancer) but at a faster rate to give a higher population turnover). In a high mortality environment, the most adaptable animals will be more successful.

However, I think this is likely to be secondary to the pressures on other survival traits that more directly increase the chances of successful reproduction.

Great answer, this makes several things clear which I didn't fully grasp before. However, what evidence is there for 'population-level' natural selection (the last section of your answer)? It sounds like the sort of 'group selection' explanation which has been disproved by the modern gene-centred understanding of evolution.
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Richard Smith-UnnaJul 12 '12 at 11:19

@RichardSmith I'll try to find where I read that last section, but I don't see how group selection can been disproven in that manner. Evolution acts on the genes, not on individuals. If it is advantageous for a group of genes (e.g. the genome of a species) to have a high turnover, giving greater evolvability (i.e. more chance of survival in changing conditions) then it will come at the 'cost' (shorter life) to the individual.
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LukeJul 12 '12 at 11:34

That's exactly what I meant, natural selection is acting on the gene, not the population. It only matters whether any given mutation affecting evolvability leads to more copies of the gene containing it. There is no such thing as group selection, it's a relic of the Modern Synthesis of the 50s and 60s. I think perhaps you were unintentionally using group selection language but you were describing an effect of gene selection. The population doesn't care about the turn-over of its members - it's just an arbitrary group.
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Richard Smith-UnnaJul 12 '12 at 12:48

So, if something is only advantageous at the population level, it won't be selected for, which is why this sentence doesn't make sense: "This in turns increases their evolvability - clearly advantageous at the population, not individual, level."
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Richard Smith-UnnaJul 12 '12 at 12:50

@RichardSmith right OK, I see where you're coming from, but not how to re-word what I am saying; that a trait that increases the relative (strictly Darwinian) 'fitness' of a species can be selected for at the 'cost' of a shorter life to an individual organism. This may be disadvantageous in some terms, because they will have less time to reproduce, however higher population turnover will be advantageous in fast-changing conditions.
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LukeJul 12 '12 at 13:47